Sildenafil previne a nefropatia induzida por contraste em ratos wistar

Abstract

Despite being one of the most common causes of acute renal failure in hospitalized patients, the contrast-induced nephropathy (CIN) is a common but poorly understood problem and does not have an appropriate treatment. Studies report on the antioxidant action of phosphodiesterase 5 inhibitors. Therefore, we investigated if sildenafil can prevent or ameliorate kidney dysfunction in an experimental model of CIN in rats. Male Wistar rats (290-390 g) were treated for 7 days by gavage with sildenafil (50 mg/kg/day) or vehicle (2ml/kg/day). The acute nephropathy was induced by water restriction (24 hr), L-NAME and indomethacin injection (10mg / kg i.p.) and contrast medium injection (iohexol 3mg/Kg i.v.) or saline, resulting in the following experimental groups: control, CIN, CIN + sildenafil. After, was made the analysis of renal function including assessment of the glomerular filtration rate (GFR), renal blood flow (RBF), renal plasma flow (RPF) and renal vascular resistance (RVR) by determining the clearance of inulin and para-aminohippurate, and investigation of oxidative stress at the molecular level (flow cytometry). Values are expressed as means ± S.E.M. one-way ANOVA followed by Tukey´s post hoc test. A value of p<0.05 was regarded as statistically significant. Contrast administration has resulted in decline in GFR (control: 8.53 ± 0.55; CIN: 3.77 ± 0.26*; CIN + S: 6.77 ± 0.39*# mL/min/Kg), RPF(control: 20.04 ± 0.9; CIN: 9.59 ± 0.38*; CIN + S:13.18 ± 0.26* # mL/min/Kg) and RBF(control: 35.01 ± 2.02, ± 0.67*; CIN: 20,36; NIC + S: 22.46 ± 0.8* # mL/min/Kg) and increased RVR (control: 3.59 ± 0.46; CIN: 7.72 ± 0.31 *; CIN + S: 4.86 ± 0.17# a.u), which was prevented by treatment with sildenafil. Therefore, sildenafil may be a promising therapeutic agent for the prevention and / or treatment of renal dysfunction induced by contrast.